title: Spike-timing-related plasticity is preserved in Parkinson's disease and is enhanced by dopamine: evidence from transcranial magnetic stimulation.
abstract: We sought to investigate the effects of dopamine on motor cortical plasticity in Parkinson's disease (PD) using a novel interventional transcranial magnetic stimulation protocol that targets spike-timing-dependent plasticity (iTMS). Six patients (3F, mean age 62 years) with mild-moderate PD (mean disease duration 6 years, UPDRS-off 13, UPDRS-on 3, H&Y stage 2, daily levodopa dosage 450 mg) were studied off and on levodopa on separate days. Paired TMS pulses at resting motor threshold with an inter-stimulus interval of 1.5 ms were given over the hand area of the motor cortex for 20 min at 0.2 Hz. Single-pulse motor evoked potential (MEP) amplitude and visually cued simple reaction time (SRT) were measured before and after iTMS. When on levodopa, MEP amplitude increased to 278+/-36% of baseline (p<0.01), and when off levodopa to 157+/-13% of baseline (p=0.02). All patients showed a significantly greater increase in MEP amplitude when on levodopa than off levodopa (p=0.01). SRT was reduced to 95% baseline after iTMS off levodopa (p=0.02), but did not change on levodopa. These findings indicate that motor cortex plasticity to iTMS is preserved in mild-moderate PD. The effects of this spike-timing-related TMS protocol on cortical excitability were consistent and were enhanced by levodopa. The results support the important role of dopamine in regulating synaptic plasticity and justify a larger crossover study to assess the therapeutic effects of iTMS in PD.
authors.affiliation: Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Australia. jrod@cyllene.uwa.edu.au
authors.forename: Julian P
authors.initials: JP
authors.lastname: Rodrigues
authors.forename: Susan E
authors.initials: SE
authors.lastname: Walters
authors.forename: Rick
authors.initials: R
authors.lastname: Stell
authors.forename: Frank L
authors.initials: FL
authors.lastname: Mastaglia
authors.forename: Gary W
authors.initials: GW
authors.lastname: Thickbroom
mesh_terms: D000212:Acyclovir / Q000031:analogs & derivatives; D000368:Aged; D000704:Analysis of Variance; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology / Q000627:therapeutic use; D004558:Electric Stimulation / Q000379:methods; D019054:Evoked Potentials, Motor / Q000187:drug effects / Q000502:physiology*; D005260:Female; D018698:Glutamic Acid / Q000031:analogs & derivatives / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007980:Levodopa / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000187:drug effects / Q000503:physiopathology*; D010300:Parkinson Disease / Q000188:drug therapy / Q000503:physiopathology*; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D050781:Transcranial Magnetic Stimulation
chemical_list: D015259:Dopamine Agents; C495023:gamma-glutamylacyclovir; D018698:Glutamic Acid; D007980:Levodopa; D004298:Dopamine; D000212:Acyclovir